Gonadorelin

What it is

Gonadorelin is a 10-amino-acid peptide that is identical to the hormone your hypothalamus makes to run the reproductive system. The hypothalamus releases GnRH in short pulses, the pituitary responds by releasing LH and FSH, and those hormones tell the testes or ovaries to work.

It has been used as a diagnostic test for pituitary function, and in pump form to treat some forms of hypogonadotropic hypogonadism and to induce ovulation. Neither of those uses is common any more, and the brand products (such as Factrel and Lutrepulse) have largely been withdrawn in many markets.

In the TRT world it is used as an alternative to HCG to keep the testes working while on testosterone. That use is off-label and the evidence for it is thin.

History

GnRH was isolated and its structure worked out by Andrew Schally and Roger Guillemin in the early 1970s, and they shared the 1977 Nobel Prize in Physiology or Medicine. Gonadorelin has been used clinically since then, mainly for testing and pump therapy.

How it works

GnRH acts on the pituitary to release LH and FSH, but only when it arrives in pulses (roughly every 60-120 minutes in nature). A steady, continuous signal does the opposite: the pituitary desensitises and LH and FSH fall. This is how related drugs such as leuprorelin shut down hormones in prostate cancer. Gonadorelin has a very short half-life, so a single injection acts as one pulse.

Dosage

• There is no standard off-label dose. Community use for men on TRT commonly reports 100-200 mcg subcutaneously, two to three times a week, sometimes more often.
• Because the half-life is only minutes, a single weekly injection works as one brief pulse and may not mimic anything close to natural rhythm. This is why clinical use relied on pumps giving small pulses every 90 minutes or so.
• Taking larger doses more often does not improve it. Continuous stimulation can have the opposite effect to the one you want.
• Whether gonadorelin injections reliably preserve testicular function on TRT has not been properly tested in trials.

How it is taken

• Subcutaneous injection into belly fat with a 29-31G insulin syringe.
• Rotate sites. Some people inject daily at low dose, others two or three times a week; no schedule has proven superior.

How to reconstitute

• 2 mg vial: add 2 ml bacteriostatic water to get 1 mg/ml. That is 10 mcg per unit on a 1 ml syringe, so a 100 mcg dose is 10 units and 200 mcg is 20 units.
• 5 mg vial: add 2.5 ml to get 2 mg/ml, which is 20 mcg per unit. 100 mcg is 5 units and 200 mcg is 10 units.
• Add water slowly down the inside of the vial and swirl gently. Do not shake.

How it should arrive

Sealed glass vial with a crimped cap and a small white cake or fluffy powder at the bottom.

How it should look once reconstituted

Clear and colourless. If it is cloudy, has flakes or residue, do not use it.

What to expect, and when

• In a diagnostic test, LH rises within 30-60 minutes of injection.
• For testicle size and function on TRT, any effect is reported over weeks, but this is anecdotal.
• If you notice no change in testicular size or bloods after 8-12 weeks, it may simply not be working for you.

Side effects

• Injection-site redness or soreness.
• Headache, flushing, nausea or lightheadedness, usually mild.
• Rarely: allergic reactions or anaphylaxis have been reported with GnRH products.
• Changes in mood or libido linked to hormone shifts.

Risks

• Evidence in humans for the TRT-adjunct use is minimal. Much of the confidence comes from the logic of the mechanism, not from trials.
• If given continuously or too frequently, it can suppress rather than stimulate the system.
• Quality varies widely among research suppliers. Third-party testing is worth looking for.
• It is a prescription-only medicine where licensed. Research-vial sales fall outside regulatory oversight.
• If you are using it for fertility reasons, get a proper workup. It should not replace a prescriber.

Potential gains

• A diagnostic test of pituitary response, which is its best-established use.
• Pump-based therapy for some patients with hypothalamic hypogonadism, in specialist care.
• Possible maintenance of testicular function on TRT, supported mostly by mechanism and anecdote.

Other useful information

In practice, HCG has the longer evidence track record for keeping the testes working on TRT, and its longer half-life makes injections every few days sensible. Gonadorelin is an option for people who cannot get or tolerate HCG, but expect to rely on your own bloods to tell you if it is working.